A high blood endocan profile during COVID-19 distinguishes moderate from severe acute respiratory distress syndrome

Abstract

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Endocan is expressed by the lung endothelial cells and upregulated by pro-inflammatory conditions. Because elevated pro-inflammatory cytokines are hallmarks of severe SARS-CoV-2 infection [1], and that the lung is the organ preferentially affected, we measured endocan in patients with COVID-19 pneumonia. This retrospective study was conducted between March 12 and April 20, 2020, and approved by the local ethics committee of the Foch Hospital (20-07-15). Seventy-four patients with COVID-19 pneumonia confirmed by RT-PCR were enrolled. According to the Berlin definition of acute respiratory distress syndrome (ARDS), patients were categorized into non-ARDS, mild/moderate ARDS, and severe ARDS. At the admission complete blood count, biochemical and coagulation parameters were measured. Endocan and cathepsin G-cleaved endocan (p14) concentrations were measured on baseline and during the hospitalization. Plasmatic endocan cleavage ratio (ECR) was calculated as plasma p14/(endocan + p14) ratio. Healthy hospital workers served as group of control. Baseline characteristics and clinical outcomes are summarized in Table 1. Patients with ARDS had significantly higher CRP (176 mg/L [IQR: 133–270] vs 141 mg/L [IQR: 88–187], p = 0.0122), and higher d-dimers (1.843 mg/L [IQR: 0.579–7.134] vs 0.771 mg/L [IQR: 0.535–1.374], p = 0.0472), had greater lung parenchyma involvement assessed by the CT score (4 [4, 5] vs 3 [2–4], p = 0.0016) and stay hospitalized for longer than non-ARDS group (25 days [IQR: 14–38] vs 12 days [IQR: 7–17], p < 0.0001). The mortality rate was also higher in patients with ARDS than non-ARDS group (43% vs 5%, p < 0.0001) (Table 1). At admission, endocan levels measured in 59/74 (84%) patients were significantly increased in patients with COVID-19 compared to controls (3.4 ng/mL [IQR: 1.8–7.5] vs 1.6 ng/mL [IQR: 1.0–2.1], respectively, p = 0.0031) (Fig. 1a). There was no significant difference between patients who developed ARDS and those who have not (3.7 [2.8–9.6] ng/mL vs 3.2 [1.5–5.7] ng/mL, respectively, p = 0.2231) (Fig. 1b). Endocan was negatively correlated with the platelets (Spearman’s correlation coefficient r = − 0.3681, p = 0.0041). When plasma samples were available in patients with ARDS, endocan concentrations were measured during the hospitalization. Patients with mild/moderate ARDS had a significant increase in endocan levels at days 3–4 (p = 0.0084) and days 5–6 (p = 0.0107) compared to those measured at days 1–2 (Fig. 1c). No increase was observed in patients with severe ARDS (Fig. 1c). This discrepancy was not due to an increase in cleavage of endocan since the ECR remained similar whatever the severity of ARDS or the hospitalization day (not shown). ECR at admission was positively correlated with the Von Willebrand antigen (r = 0.3047, p = 0.0418). ARDS was already present at admission in 15/37 (40%). Twelve (32%) patients developed ARDS within 48 h, whereas 10 (27%) patients developed ARDS between the 3rd and 7th day of hospitalization. After exclusion of patients with ARDS within the first 48 h, the calculated AUC of endocan was 0.7235 (p = 0.1104). Several biomarkers had already been Open Access